ABSTRACT
Increasing evidence demonstrated that the expression of Angiotensin I-Converting Enzyme type 2 (ACE2), is a necessary step for SARS-CoV-2 infection permissiveness. In the light of the recent data highlighting an association between COVID-19 and diabetes, a detailed analysis aimed at evaluating ACE2 expression pattern distribution in human pancreas is still lacking. Here, we took advantage of INNODIA network EUnPOD biobank collection to thoroughly analyse ACE2, both at mRNA and protein level, in multiple human pancreatic tissues and using several methodologies. Using multiple reagents and antibodies, we showed that ACE2 is expressed in human pancreatic islets, where it is preferentially expressed in subsets of insulin producing {beta}-cells. ACE2 is also is highly expressed in pancreas microvasculature pericytes and moderately expressed in rare scattered ductal cells. By using different ACE2 antibodies we showed that a recently described short-ACE2 isoform is also prevalently expressed in human {beta}-cells. Finally, using RT-qPCR, RNA-seq and High-Content imaging screening analysis, we demonstrated that pro-inflammatory cytokines, but not palmitate, increases ACE2 expression in the {beta}-cell line EndoC-{beta}H1 and in primary human pancreatic islets. Taken together, our data indicate a potential link between SARS-CoV-2 and diabetes through putative infection of pancreatic microvasculature and/or ductal cells and/or through direct {beta}-cell virus tropism.
ABSTRACT
The aim of the study was to assess the postpartum risk for glucose intolerance since the introduction of the 'International Association of Diabetes and Pregnancy Study Groups' (IADPSG) criteria for gestational diabetes mellitus (GDM). Studies published since 2010 were included, which evaluated the risk for type 2 diabetes mellitus (T2DM), impaired glucose tolerance (IGT), and cardiovascular (CV) events in women with previous GDM compared to normal glucose tolerant women. We included forty-three studies, evaluating 4,923,571 pregnant women of which 5.8% (284,312) had a history of GDM. Five studies used IADPSG criteria (n = 6174 women, 1314 with GDM). The overall pooled relative risk (RR) for postpartum T2DM was 7.42 (95% CI: 5.99-9.19) and the RR for postpartum T2DM with IADPSG criteria was 6.45 (95% CI: 4.74-8.77) compared to the RR of 9.08 (95% CI: 6.96-11.85; p = 0.17) for postpartum T2DM based on other diagnostic criteria. The RR for postpartum IGT was 2.45 (95% CI: 1.92-3.13), independent of the criteria used. None of the available studies with IADPSG criteria evaluated the risk for CV events. Women with a history of GDM based on the IADPSG criteria have a similarly increased risk for postpartum glucose intolerance compared to GDM based on other diagnostic criteria. More studies with GDM based on the IADPSG criteria are needed to increase the quality of evidence concerning the long-term metabolic risk.
ABSTRACT
BACKGROUND: Associations between type 2 diabetic patients and a higher risk of developing cancer have been reported worldwide. Recently, a protective effect of metformin has been described. AIM: To examine in the Belgian primary care population the relation between presence of type 2 diabetes with and without metformin treatment and the occurrence of malignancies. DESIGN OF STUDY: Retrospective cohort study, based on the Intego database, an ongoing Belgian general practice-based morbidity registry, covering 90 general practitioners and including about 1.5 million patient-years between 1994 and 2008. METHOD: Cox proportional hazard analysis comparing emergence of malignancy in patients with and without type 2 diabetes, and among patients with diabetes comparing emergence of malignancy in those treated with various antidiabetic drugs. RESULTS: Malignancies occurred more in type 2 diabetic patients compared to non-diabetic controls (HR=1.84; 95% CI=1.51-2.24), adjusted for age, gender and weight. Treatment with both metformin and 'other' antidiabetic agents was related to decreased cancer risk (HR=0.24 and 0.22) compared to diet only in men but not in women. CONCLUSION: In this Belgian primary care setting, diabetic patients have higher cancer prevalences than non-diabetic patients. Moreover, in diabetic men, not only metformin but also other antidiabetic agents were associated with lower cancer risks.
